Dal Magro Roberta, Vitali Agostina, Fagioli Stefano, Casu Alberto, Falqui Andrea, Formicola Beatrice, Taiarol Lorenzo, Cassina Valeria, Marrano Claudia Adriana, Mantegazza Francesco, Anselmi-Tamburini Umberto, Sommi Patrizia, Re Francesca
BioNanoMedicine Center NANOMIB, School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
Department of Chemistry, University of Pavia, 27100 Pavia, Italy.
Antioxidants (Basel). 2021 Feb 9;10(2):266. doi: 10.3390/antiox10020266.
Vascular oxidative stress is considered a worsening factor in the progression of Alzheimer's disease (AD). Increased reactive oxygen species (ROS) levels promote the accumulation of amyloid-β peptide (Aβ), one of the main hallmarks of AD. In turn, Aβ is a potent inducer of oxidative stress. In early stages of AD, the concomitant action of oxidative stress and Aβ on brain capillary endothelial cells was observed to compromise the blood-brain barrier functionality. In this context, antioxidant compounds might provide therapeutic benefits. To this aim, we investigated the antioxidant activity of cerium oxide nanoparticles (CNP) in human cerebral microvascular endothelial cells (hCMEC/D3) exposed to Aβ oligomers. Treatment with CNP (13.9 ± 0.7 nm in diameter) restored basal ROS levels in hCMEC/D3 cells, both after acute or prolonged exposure to Aβ. Moreover, we found that the extent of CNP uptake by hCMEC/D3 was +43% higher in the presence of Aβ. Scanning electron microscopy and western blot analysis suggested that changes in microvilli structures on the cell surface, under pro-oxidant stimuli (Aβ or HO), might be involved in the enhancement of CNP uptake. This finding opens the possibility to exploit the modulation of endothelial microvilli pattern to improve the uptake of anti-oxidant particles designed to counteract ROS-mediated cerebrovascular dysfunctions.
血管氧化应激被认为是阿尔茨海默病(AD)进展中的一个恶化因素。活性氧(ROS)水平升高会促进淀粉样β肽(Aβ)的积累,Aβ是AD的主要特征之一。反过来,Aβ又是氧化应激的强效诱导剂。在AD的早期阶段,观察到氧化应激和Aβ对脑微血管内皮细胞的共同作用会损害血脑屏障功能。在这种情况下,抗氧化化合物可能具有治疗益处。为此,我们研究了氧化铈纳米颗粒(CNP)对暴露于Aβ寡聚体的人脑微血管内皮细胞(hCMEC/D3)的抗氧化活性。用CNP(直径13.9±0.7纳米)处理后,无论是急性还是长期暴露于Aβ,hCMEC/D3细胞中的基础ROS水平都得到了恢复。此外,我们发现,在存在Aβ的情况下,hCMEC/D3对CNP的摄取程度高出43%。扫描电子显微镜和蛋白质印迹分析表明,在促氧化刺激(Aβ或HO)下,细胞表面微绒毛结构的变化可能与CNP摄取的增强有关。这一发现为利用内皮微绒毛模式的调节来改善旨在对抗ROS介导的脑血管功能障碍的抗氧化颗粒的摄取开辟了可能性。